Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the insulin signaling pathway

Abstract

Knockout of metallothionein (MT) genes contributes to a heavier body weight in early life and the potential to become obese through the intake of a high fat diet (HFD) in mice. It has thus been suggested that MT genes regulate the formation of adipose tissue, which would become the base for later HFD-induced obesity. We evaluated the fat pads of mice during the lactation stage. The fat mass and adipocyte size of MT1 and MT2 knockout mice were greater than those of wild type mice. Next, we assayed the ability of small interfering RNA (siRNA) to silence MT genes in the 3T3-L1 cell line. The expressions of MT1 and MT2 genes were transiently upregulated during adipocyte differentiation, and the siRNA pretreatment led to the suppression of the expression of both MT mRNAs and proteins. The MT siRNA promoted lipid accumulation in adipocytes and caused proliferation of post-confluent preadipocytes; these effects were suppressed by an inhibitor of phosphatidylinositol 3-kinase (LY294002). In addition, MT siRNA promoted insulin-stimulated phosphorylation of Akt, a downstream kinase of the insulin signaling pathway. Enhanced lipid accumulation in 3T3-L1 cells resulting from MT-gene silencing was inhibited by pretreatment with an antioxidant, N-acetylcysteine, used as a substitute for antioxidant protein MTs. These results suggest that interference in MT expression enhanced the activation of the insulin signaling pathway, resulting in higher lipid accumulation in 3T3-L1 adipocytes.

N-Acetylcysteine Inhibits Lipids Production in Mature Adipocytes through the Inhibition of Peroxisome Proliferator-Activated Receptor 

“…Other authors that have used NAC during adipocyte differentiation, reported similar results [18,20,38,39]. Therefore, we could speculate about a possible use of this molecule as a new drug or as an adjuvant to decrease lipid content in human adipose tissue during obesity development.…”

N-acetyl cysteine can blunt metabolic and cardiovascular effects via down-regulation of cardiotrophin-1 in rat model of fructose-induced metabolic syndrome

“…In our observations, co-administration of NAC resulted in a remarkable reduction of nal body weight and body weight gain. In an in vitro study, NAC treatment to cultured adipocytes repressed lipid accumulation and ROS production [20]. Also, in experimental models of diet induced obesity, NAC supplementation exhibited weight reduction effect [21,22].…”

MiRNAs and mRNAs Analysis during Abdominal Preadipocyte Differentiation in Chickens

“…FOXOs are implicated in a broad range of cellular functions, and these are cellular properties, critical to the cell biology, including cellular differentiation, apoptosis, cell proliferation, DNA damage, and repair [42,43]. Obesity leads to the progression of insulin resistance and type II diabetes mellitus [44], and studies have reported that insulin signaling pathways regulate adiposity cell differentiation [45]. Therefore, these signaling pathways may be keys to further explore the molecular mechanisms underlying chicken adipose differentiation.…”